Reversible pH-Driven Flocculation of Amphiphilic Polyelectrolyte-Coated Nanoparticles for Rapid Filtration and Concentration

Kurt D. Ristroph, Jenna A. Ott, Luqman A. Issah, Brian K. Wilson, Amila Kujović, Madeleine Armstrong, Sujit S. Datta, Robert K. Prud’homme

Research output: Contribution to journalArticlepeer-review

Abstract

Nanoformulating poorly water-soluble drugs is attractive for improving oral dissolution kinetics, but concentrating and drying dilute nanoparticle (NP) suspensions is a barrier to translation. This work describes a reversible, pH-driven flocculation technique for concentrating NPs stabilized with a carboxylic acid-bearing cellulose polymer. Lumefantrine NPs 150 nm in diameter stabilized by anionic hydroxypropylmethylcellulose acetate succinate, a Food and Drug Administration-approved pharmaceutical polymer excipient, are prepared using flash nanoprecipitation. Particles are then concentrated 50-fold by acid-induced flocculation at pH 2.0, separation (either filtration or centrifugation), and base-induced redispersion at pH 6.9, reducing the drying time 50-fold. Dried powders retain enhanced lumefantrine dissolution kinetics. Filtration efficiency is assessed, and flocculation is found to improve NP retention from 3 to 85% on a 2.5 μm filter. The kinetics of flocculation and the fractal nature of the flocs are studied using confocal microscopy and agree closely with a diffusion-limited aggregation model. These results demonstrate a proof of concept that reversible flocculation is a facile method for separating amphiphilic polyelectrolyte-coated NPs from suspension for advanced processing.

Original languageEnglish (US)
Pages (from-to)8690-8698
Number of pages9
JournalACS Applied Nano Materials
Volume4
Issue number9
DOIs
StatePublished - Sep 24 2021

All Science Journal Classification (ASJC) codes

  • Materials Science(all)

Keywords

  • FNP
  • confocal microscopy
  • flash nanoprecipitation
  • flocculation
  • lumefantrine
  • malaria
  • nanoparticle concentration
  • pH responsive
  • polyelectrolyte

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